begin showing clinical signs of illness. 2 Viral shedding begins to decrease as signs of infection appear, and has typically stopped by 7 to 10 days post-infection. 3,5,12 Treatment with steroids has been demonstrated to prolong viral shedding to as long as 2 weeks. 4 Because the newly-introduced H3N2 strain of canine influenza is an emerging disease, most dogs have no immunity against it. Therefore, virtually all exposed dogs will become infected if they are exposed to this strain. 12 All dogs are susceptible to canine influenza virus regardless of age, breed, or gender.
Approximately 80% of infected dogs will show clinical signs; these signs may vary from a mild cough to more severe cases of pneumonia requiring hospitalization. The remaining 20% of infected dogs will shed the virus without demonstrating any clinical signs of illness, 5,12 thus further contributing to the spread of the virus in a newly-exposed population. Due to the possibility of asymptomatic infection and viral shedding, any dog exposed to canine influenza should be considered potentially-contagious for 14 days. 2
CLINICAL SIGNS
Canine influenza virus replicates in all cells of the respiratory tract, from the nasal lining into the terminal airways of the lung. This viral replication leads to significant neutrophilic and monocytic rhinitis, tracheitis, bronchitis, and bronchiolitis. 3,5,12 In addition to this inflammation throughout the respiratory tract, airway epithelial cells begin to die, exposing the underlying basement membrane and impairing mucociliary clearance. 1 Accumulations of mucus and necrotic epithelial cells within the airways create an environment favorable for the growth of commensal and opportunistic bacteria, thus contributing to secondary bacterial infections. 1,12 While media reports during the 2015 Chicago H3N2 outbreak implied that this new strain of canine influenza was more severe than the previous H3N8 strain, there is no evidence to support this claim. Both strains of canine influenza are typically associated with a low mortality rate and most cases are self- limiting. 10 Although the morbidity rate of canine influenza is high (the majority of exposed dogs will become infected, even if they do not show clinical signs), the mortality rate is very low. 12 Most dogs infected with canine influenza will demonstrate mild signs of disease, indistinguishable from other common upper respiratory infections. The most commonly-reported symptom is a cough, which is identical to that seen with kennel cough or infectious tracheobronchitis except for its duration. The cough associated with canine influenza typically persists for approximately 10 to 21 days, which is significantly longer than the typical clinical course of kennel cough. 9,12 Some dogs with mild canine influenza infections may also develop serous ocular or nasal discharge, sneezing, lethargy,
low-grade fever, and/or anorexia 12 in addition to cough. Purulent nasal discharge may be observed; this is not due to the influenza infection itself but instead due to secondary bacterial infection, usually involving Pasteurella and/or mycoplasma. 12 In more severe cases, canine influenza H3N2 has been associated with high fevers (104°F to 106°F) and the development of pneumonia. Thoracic radiographs in these severely-affected cases may show evidence of consolidated lung lobes. 12 This pneumonia is felt to be largely due to secondary bacterial infection, although there are isolated reports of severe pneumonia in dogs with sterile bacterial cultures.3 This raises the possibility that the virus itself may be capable of causing significant pulmonary changes and pneumonia. Canine influenza virus associated pneumonia can be life- threatening in a small number of cases. In the 2015 Chicago outbreak, a mortality rate of approximately 5 in 1,000 dogs, or 0.05%, was observed. 9 The most severe manifestations of canine influenza have been noted in racing greyhound facilities, where significantly higher mortality rates have been reported. 12 Often, greyhounds in these settings have died acutely and necropsy revealed evidence of fibrinous pleuritis, severe bronchopneumonia, and pulmonary/ mediastinal/pleural hemorrhage. This syndrome is not fully understood, but it is felt to be due to the unique environment and physical stresses placed upon racing greyhounds. Infection with Streptococcus equi zooepidemicus may also play a role. A similar syndrome has not been reported in pet dogs. 12
DIAGNOSIS
When dogs with influenza initially present to the hospital for signs of upper respiratory disease, the first diagnostic testing to be performed will likely include a minimum database. In dogs with mild cases of influenza, without secondary bacterial pneumonia, the complete blood cell counts and serum biochemistries will typically show no abnormalities. 3,5 If a leukocytosis with neutrophilia and left shift is observed, the veterinarian should suspect pneumonia and thoracic radiographs should be performed. Radiographic findings vary in these more severe cases, ranging from mild bronchointerstitial infiltrates to generalized lung consolidation. Radiographic disease may be noted unilaterally or bilaterally, but the right middle lung lobe and caudal part of the left cranial lung lobe appear to be most commonly involved. 3,5 If canine influenza is suspected early in the course of infection (less than 4 days after the onset of clinical signs), nasal or pharyngeal swabs can be submitted for polymerase chain reaction (PCR) testing. Virus recovery rates have been noted to be higher with nasal swabs, so these samples are preferred. 4 Once obtained, these swabs can be placed into a red-top tube with a few drops of sterile saline (or in viral transport media, if available) and can be processed through commercial laboratories or shipped via overnight delivery to participating university laboratories on ice. 14 The specificity of canine influenza PCR is relatively high and false positives are rare, but false negatives can occur if swabs are collected after the time of
peak virus shedding. 12 PCR can also be used to test for canine influenza virus in the lung tissue of deceased dogs if obtained at necropsy. 4 Virus isolation is another method that can be utilized in the diagnosis of canine influenza, but again it is unlikely to be successful after the first 3 to 4 days of infection. Canine influenza viruses have been successfully isolated in embryonated eggs or cell cultures, depending on the viral strain. Like PCR, virus isolation can provide false negative results if samples are not collected within the early stages of clinical signs, as diagnosis is based on active viral shedding at the time of sample collection. Because canine influenza is often not suspected as a cause of upper respiratory illness until later in the course of disease, the utility of virus isolation is low in a clinical setting. 4 Antigen-capture enzyme-linked immunosorbent assay (ELISA) tests do not seem to be useful in testing individual dogs, likely due to the small amounts of virus shed outside of the early clinical period. These tests have a lower reported sensitivity and specificity than PCR and virus isolation, making them unreliable in testing of individual dogs. Antigen-capture ELISA may, however, be useful during investigations of outbreaks involving large numbers of dogs, due to their ease of use. 4 If a dog has been showing upper respiratory signs for more than 4 days, serologic testing is the preferred means of diagnosis. These tests utilize hemagglutination inhibition to assess for the
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